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Interferon-microRNA signalling drives liver precancerous lesion formation and hepatocarcinogenesis.
Yang, Yingcheng; Lin, Ximeng; Lu, Xinyuan; Luo, Guijuan; Zeng, Tao; Tang, Jing; Jiang, Feng; Li, Liang; Cui, Xiuliang; Huang, Wentao; Hou, Guojun; Chen, Xin; Ouyang, Qing; Tang, Shanhua; Sun, Huanlin; Chen, Luonan; Gonzalez, Frank J; Wu, Mengchao; Cong, Wenming; Chen, Lei; Wang, Hongyang.
Afiliación
  • Yang Y; International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, China Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
  • Lin X; International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, China Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
  • Lu X; Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
  • Luo G; International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, China National Center for Liver Cancer, Shanghai, China.
  • Zeng T; Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
  • Tang J; International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, China National Center for Liver Cancer, Shanghai, China.
  • Jiang F; International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, China.
  • Li L; International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, China National Center for Liver Cancer, Shanghai, China.
  • Cui X; International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, China National Center for Liver Cancer, Shanghai, China.
  • Huang W; International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, China.
  • Hou G; International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, China.
  • Chen X; International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, China.
  • Ouyang Q; International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, China.
  • Tang S; International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, China.
  • Sun H; International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, China.
  • Chen L; Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
  • Gonzalez FJ; Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
  • Wu M; Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
  • Cong W; Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
  • Chen L; International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, China National Center for Liver Cancer, Shanghai, China Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Insti
  • Wang H; International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, China National Center for Liver Cancer, Shanghai, China State Key Laboratory for Oncogenes and Related Genes, Cancer Institute of RenJi Hospital, Shang
Gut ; 65(7): 1186-201, 2016 07.
Article en En | MEDLINE | ID: mdl-26860770
OBJECTIVE: Precancerous lesion, a well-established histopathologically premalignant tissue with the highest risk for tumourigenesis, develops preferentially from activation of DNA damage checkpoint and persistent inflammation. However, little is known about the mechanisms by which precancerous lesions are initiated and their physiological significance. DESIGN: Laser capture microdissection was used to acquire matched normal liver, precancerous lesion and tumour tissues. miR-484(-/-), Ifnar1(-/-) and Tgfbr2(△hep) mice were employed to determine the critical role of the interferon (IFN)-microRNA pathway in precancerous lesion formation and tumourigenesis. RNA immunoprecipitation (RIP), pull-down and chromatin immunoprecipitation (ChIP) assays were applied to explore the underlying mechanisms. RESULTS: miR-484 is highly expressed in over 88% liver samples clinically. DEN-induced precancerous lesions and hepatocellular carcinoma were dramatically impaired in miR-484(-/-) mice. Mechanistically, ectopic expression of miR-484 initiates tumourigenesis and cell malignant transformation through synergistic activation of the transforming growth factor-ß/Gli and nuclear factor-κB/type I IFN pathways. Specific acetylation of H3K27 is indispensable for basal IFN-induced continuous transcription of miR-484 and cell transformation. Convincingly, formation of precancerous lesions were significantly attenuated in both Tgfbr2(△hep) and Ifnar1(-/-) mice. CONCLUSIONS: These findings demonstrate a new protumourigenic axis involving type I IFN-microRNA signalling, providing a potential therapeutic strategy to manipulate or reverse liver precancerous lesions and tumourigenesis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Lesiones Precancerosas / Transducción de Señal / Transformación Celular Neoplásica / Carcinoma Hepatocelular / MicroARNs / Neoplasias Hepáticas Idioma: En Revista: Gut Año: 2016 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Lesiones Precancerosas / Transducción de Señal / Transformación Celular Neoplásica / Carcinoma Hepatocelular / MicroARNs / Neoplasias Hepáticas Idioma: En Revista: Gut Año: 2016 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido